期刊
ACTA BIOMATERIALIA
卷 102, 期 -, 页码 298-314出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2019.11.005
关键词
Bacterial cellulose; Hyperbranched cationic polysaccharide derivatives; RNA interference; Matrix metalloproteinase 9; Diabetic wound healing
资金
- Key Research and Development Projects of the Ministry of Science and Technology [2016YFC0901204]
- National Natural Science Foundation of China [81500640, 81770827, 81670764, 81870571]
- Science and technology projects of Guang Dong Province [201613020238001]
- Guangdong Science and Technology Development Project [2017B020209002]
- Special fund for science and technology development of Guang Dong Province [2016A01010301]
- Key project of Guangdong Natural Science Foundation of China [2017B030311007]
- 973 Program of China [2015CB755500]
- Special Funds for Public Welfare Research and Capacity Building of Guangdong Province in China [2014A010105025, 2016A020222017]
- Yixian Excellent Young Medical Talents Project
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes
The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro, while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. Statement of significance In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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